While all cancer patients could potentially benefit from earlier detection methods the development of new screening methods/assays for epithelial ovarian cancer (EOC) is unique in this regard. EOC is the fourth leading cause of death in American women due to our present inability to detect early stage (I) disease. The purpose of this project is to apply state-of-the-art innovative sonographic technologies to achieve the accurate detection of early stage epithelial ovarian cancer (EOC). Recent sonographic developments involving improved scanning with harmonics and pulse inversion and the use of contrast agents justify the hope that the sonographic depiction of the aberrant tumor microvascularity will provide visualization of the vascular changes associated with early stage disease. Contrast-enhanced sonography also affords characterization of microvascularity perfusion by assessment of time-activity curves. Our recent work with contrast enhanced sonography of implanted tumors revealed significant potential for the sonographic distinction between benign vs. malignant ovarian lesions based on the depiction of the microvascularity. We propose to use pulse inversion harmonic microvascular imaging technology to depict differences between the microvascularity of benign and malignant ovarian lesions (Aim 1, R21). Microvascularity imaging involves the acquisition of contrast-enhanced images, some stored as a maximum intensity projection. A specifically designed software program will quantify the independent images and produce the time-intensity curves. Low mechanical index real time imaging will show the tumor's microvascular patterns. Perfusion can be studied by assessing the replenishment curve after a high mechanical index flash of microbubble disruption. Thus, this research study will utilize the recently developed techniques for sonographic depiction to assess microvascularity associated with early stage EOC (R33). In Aim 2 we will evaluate the clinical utility of microvascular imaging in those high-risk women receiving prophylactic surgical extirpation of both ovaries and fallopian tubes. In Specific Aim 3 we will use our recently identified ovarian cancer specific serum biomarkers, in combination with this newly developed diagnostic imaging technology to achieve detection of early stage disease. These studies to accurately detect early stage EOC, if successful will have a significant impact on the morbidity and mortality associated with EOC.